Stem Cell Reviews and Reports最新文献

{"title":"Improving the Wound Healing Process: Pivotal role of Mesenchymal stromal/stem Cells and Immune Cells.","authors":"Mahvash Sadeghi, Asma Moghaddam, Amir Mohammad Amiri, Kianush Charoghdoozi, Mojgan Mohammadi, Sajad Dehnavi, Mahmoud Orazizadeh","doi":"10.1007/s12015-025-10849-0","DOIUrl":"10.1007/s12015-025-10849-0","url":null,"abstract":"<p><p>Wound healing, a physiological process, involves several different types of cells, from immune cells to non-immune cells, including mesenchymal stromal/stem cells (MSC), and their interactions. Immune cells including macrophages, neutrophils, dendritic cells (DC), innate lymphoid cells (ILC), natural killer (NK) cells, and B and T lymphocytes participate in wound healing by secreting various mediators and interacting with other cells. MSCs, as self-renewing, fast proliferating, and multipotent stromal/stem cells, are found in a wide variety of tissues and critically involved in different phases of wound healing by secreting various molecules that help to improve tissue healing and regeneration. In this review, first, we described the four main phases of wound healing, second, we reviewed the function of MSCs, MSC secretome and immune cells in improving the progress of wound repair (mainly focusing on skin wound healing), third, we explained the immune cells/MSCs interactions in the process of wound healing and regeneration, and finally, we introduce clinical applications of MSCs to improve the process of wound healing.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"680-697"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Cell Fate Determining Transcription Factors for Generating Brain Endothelial Cells.","authors":"Roya Ramezankhani, Jonathan De Smedt, Burak Toprakhisar, Bernard K van der Veer, Tine Tricot, Gert Vanmarcke, Bradley Balaton, Leo van Grunsven, Massoud Vosough, Yoke Chin Chai, Catherine Verfaillie","doi":"10.1007/s12015-025-10842-7","DOIUrl":"10.1007/s12015-025-10842-7","url":null,"abstract":"<p><p>Reliable models of the blood-brain barrier (BBB), wherein brain microvascular endothelial cells (BMECs) play a key role in maintenance of barrier function, are essential tools for developing therapeutics and disease modeling. Recent studies explored generating BMEC-like cells from human pluripotent stem cells (hPSCs) by mimicking brain-microenvironment signals or genetic reprogramming. However, due to the lack of comprehensive transcriptional studies, the exact cellular identity of most of these cells remains poorly defined. In this study we aimed to identify the most likely master transcription factors (TFs) for inducing brain endothelial cell (EC) fate and assess the transcriptomic changes following their introduction into immature ECs. Therefore, we first generated PSC-derived immature ECs by transient overexpression of the TF, ETV2. Subsequently, by performing an extensive meta-analysis of transcriptome studies of brain and non-brain ECs, 12 candidate TFs were identified, which might fate immature ECs towards cells with brain EC features. Following combinatorial overexpression of these 12 TFs tagged with unique barcodes, single cell transcriptomics identified a subset of transduced cells that resembled mid-gestational human brain ECs. Assessment of the TF barcodes present in these cells revealed significant enrichment of the TFs ZIC3, TFAP2C, TFAP2A, and DLX2. These TFs might be useful to fate PSC-EC to BMEC-like cells, which could be incorporated in human in vitro BBB models.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"744-766"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stem Cell-Derived Extracellular Vesicles for Acute Pancreatitis: a Systematic Review and Meta-analysis of Preclinical Studies.","authors":"Yinghui Hong, Mingliang Ye, Junshi Wang, Lei Huang","doi":"10.1007/s12015-025-10852-5","DOIUrl":"10.1007/s12015-025-10852-5","url":null,"abstract":"<p><strong>Background: </strong>Several studies have reported the effectiveness of stem cell-derived extracellular vesicles (SC-EVs) in disease treatment. However, the efficacy of SC-EVs for severe acute pancreatitis (SAP) remains uncertain. This systematic review aimed to analyze and evaluate the effect of SC-EVs in the treatment of SAP in animal models by summarizing data from published studies.</p><p><strong>Methods: </strong>We searched Pubmed, Embase, and Web of Science databases to identify preclinical studies investigating the therapeutic effect of SC-EVs on SAP. The primary outcome was the histopathological scores of pancreatic tissues, including inflammation, edema, and necrosis. Other outcome measures included levels of amylase, IL-6, IL-10, and TNF-α. Eligible studies were selected based on the inclusion and exclusion criteria. SYRCLE checklist was adopted to assess the quality and bias risks of included studies. Mean differences and 95% confidence intervals were calculated using the inverse variance method with a random effects model. All statistical analyses were performed using RevMan 5.3 software.</p><p><strong>Results: </strong>A total of 8 studies including 126 animals were included. The results of meta-analysis revealed that SC-EVs treatment significantly reduced pancreatic histopathologic scores (total score: MD = -5.17, 95% CI: -5.79, -4.55; inflammation score: MD = -1.44, 95% CI: -1.70, -1.19; edema score: MD = -1.42, 95% CI: -1.75, -1.09; necrosis score: MD = -1.42, 95% CI: -1.80, -1.04), inhibited pro-inflammatory factor release (IL-6: SMD = -3.20, 95% CI: -4.51, -1.88; TNF-α SMD = -5.18, 95% CI: -6.96, -3.40), and enhancing the release of anti-inflammatory factors (IL-10 SMD = 4.15, 95% CI: 2.49, 5.81). Further subgroup analyses displayed SC-EVs treatment obviously attenuated animal pancreatic pathologic injury in traumatic pancreatitis and drug-induced acute pancreatitis, and the effect of SC-EVs to inhibit TNF-α secretion in the drug-induced SAP model was correlated with the dose of SC-EVs injection.</p><p><strong>Conclusions: </strong>This meta-analysis displayed that SC-EVs were correlated with SAP injury alleviation and pancreas function reservation. Research into the treatment of SAP with SC-EVs is still in its early stage, necessitating further comprehensive investigations in the future to elucidate the therapeutic mechanisms of SC-EVs and their potential application in SAP.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"767-778"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stem Cell Therapy Modulates Molecular Cues of Vasogenic Edema Following Ischemic Stroke: Role of Sirtuin-1 in Regulating Aquaporin-4 Expression.","authors":"Aishika Datta, Bijoyani Ghosh, Anirban Barik, Gautam Karmarkar, Deepaneeta Sarmah, Anupom Borah, Shailendra Saraf, Dileep R Yavagal, Pallab Bhattacharya","doi":"10.1007/s12015-025-10846-3","DOIUrl":"10.1007/s12015-025-10846-3","url":null,"abstract":"<p><strong>Background: </strong>Conventional post-stroke edema management strategies are limitedly successful as in multiple cases of hemorrhagic transformation is being reported. Clinically, acute-ischemic-stroke (AIS) intervention by endovascular mesenchymal stem cells (MSCs) have shown benefits by altering various signaling pathways. Our previous studies have reported that intra-arterial administration of 1*10⁵ MSCs (IA-MSCs) were beneficial in alleviating post-stroke edema by modulating PKCδ/MMP9/AQP4 axis and helpful in preserving the integrity of blood-brain-barrier (BBB). However, the role of mitochondrial dysfunction and ROS generation post-AIS cannot be overlooked in context to the alteration of the BBB integrity and edema formation through the activation of inflammatory pathways. The anti-inflammatory activity of IA-MSCs in stroke has been reported to be regulated by sirtuin-1 (SIRT-1). Hence, the relationship between SIRT-1 and AQP4 towards regulation of post-stroke edema needs to be further explored. Therefore, the present study deciphers the molecular events towards AQP4 upregulation, mitochondrial dysfunction and BBB disruption in context to the modulation of SIRT-1/PKCδ/NFκB loop by IA-MSCs administration.</p><p><strong>Methods: </strong>Ovariectomized SD rats were subjected to focal ischemia. SIRT-1 activator, SIRT-1 inhibitor, NFkB inhibitor and IA-MSCs were administered at optimized dose. At 24 h of reperfusion, behavioral tests were performed, and brains were harvested following euthanasia for molecular studies.</p><p><strong>Results: </strong>IA-MSCs downregulated AQP4, PKCδ and NFkB expression, and upregulated SIRT-1 expression. SIRT-1 upregulation renders mitochondrial protection via reduction of oxidative stress resulting in BBB protection.</p><p><strong>Conclusion: </strong>IA-MSCs can modulate SIRT-1 mediated AQP4 expression via mitochondrial ROS reduction and modification of NFkB transcriptional regulation.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"797-815"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"It's Not Just About Speed: Single-Cell Tracking Reveals Changes in MSC Motility Associated with Replicative Senescence.","authors":"Anastasiya V Lukacheva, Mikhail I Bogachev, Anastasiya S Musorina, Darya V Kriger, Galina G Poljanskaya, Danila E Bobkov","doi":"10.1007/s12015-025-10868-x","DOIUrl":"https://doi.org/10.1007/s12015-025-10868-x","url":null,"abstract":"<p><p>Mesenchymal stem cells, cultured in 2D, are motile fibroblast-like cells with a well-developed actin cytoskeleton. In this study, we analyzed changes in cell motility during long-term cultivation accompanied by replicative senescence (RS) for DF2 and MSCWJ-1 cell lines derived from various sources and donors of different age under both normal and inflammatory conditions, the latter obtained by treatment with lysophosphatidic acid (LPA). Our results indicate that RS is associated with non-stationary alterations in the average migration speed: while the median speed derived from single-cell tracking is unaffected by the senescence stage, the average speed in young cells is enhanced due to the contribution of a subpopulation of fast-moving cells. The sensitivity of cell motility metrics to the impact of LPA varied depending on their origin, with the most pronounced effects observed during the initial passages. Using multivariate statistical analysis, we have shown explicitly that the common motility metrics (average and maximum speed, distance, sinuosity of trajectories, etc.) are associated with the passage, thus clearly reflecting senescence effect. Altogether, our results indicate that cell motility exhibits complex alterations with RS, with multiple metrics besides the average speed being affected and associated with their RS stage.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Exosomal miRNAs in Female Infertility: Therapeutic Potential and Mechanisms of Action.","authors":"Waleed Al Abdulmonem, Marya Ahsan, Ayaz Khurram Mallick, Asma'a H Mohamed, Hisham Ali Waggiallah, Alaa Shafie, Hassan Swed Alzahrani, Amal Adnan Ashour, Safia Obaidur Rab, Mohammed Tarek Mirdad, Hatim T O Ali","doi":"10.1007/s12015-025-10869-w","DOIUrl":"https://doi.org/10.1007/s12015-025-10869-w","url":null,"abstract":"<p><p>Reproductive disorders, including preeclampsia (PE), endometriosis, premature ovarian failure (POF), and polycystic ovary syndrome (PCOS), present substantial challenges to women's reproductive health. Exosomes (EXOs) are cell-derived vesicles containing molecules that influence target cells' gene expression and cellular behavior. Among their cargo, microRNAs (miRNAs)-short, non-coding RNAs typically 19-25 nucleotides in length-play a crucial role in post-transcriptional gene regulation and have been extensively studied for their therapeutic potential. miRNAs are considered therapeutic targets because they regulate key cellular pathways such as proliferation, apoptosis, angiogenesis, and tissue repair. This review examines the role of exosomal miRNAs from sources such as mesenchymal stem cells (MSCs), plasma, and amniotic fluid in female reproductive disorders, including PE, POF, PCOS, and endometriosis. We discuss their biological origins, mechanisms of miRNA sorting and packaging, and their therapeutic applications in modulating disease progression. By categorizing miRNAs according to their beneficial or detrimental effects in specific conditions, we aim to simplify the understanding of their roles in female infertility.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electron Beam Irradiation Induces Senescence Alterations in Human Adipose-Derived Stem Cells.","authors":"Denis Baranovskii, Svetlana Lyamina, Anastas Kisel, Sergey Kalish, Ekaterina Kozhevnikova, Tatiana Ivanova, Elena Isaeva, Vadim Govorun, Ilya D Klabukov","doi":"10.1007/s12015-025-10867-y","DOIUrl":"https://doi.org/10.1007/s12015-025-10867-y","url":null,"abstract":"","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes Derived from Metformin-Pretreated BMSCs Accelerate Diabetic Wound Repair by Promoting Angiogenesis Via the LINC-PINT/miR-139-3p/FOXC2 Axis.","authors":"Xiaobao Gu, Teng Li, Xiangyang Yin, Pengbo Zhai, Deyu Jiang, Ding Sun, Hongxu Yan, Bing Wang","doi":"10.1007/s12015-025-10860-5","DOIUrl":"https://doi.org/10.1007/s12015-025-10860-5","url":null,"abstract":"<p><p>Chronic trauma is a prevalent and significant complication of diabetes. Mesenchymal stem cell(MSC)-derived exosomes (Exos) have been reported to accelerate the healing of chronic diabetic wounds. MSCs pretreated with chemical or biological factors were reported to enhance the biological activity of MSC-derived exosomes. Hence, this study investigated the role of exosomes derived from bone marrow mesenchymal stem cells (BMSCs) pretreated with metformin (MET) on diabetic wound healing. The results showed that MET-Exos promoted endothelial cell migration, tube formation, and angiogenesis, leading to accelerated wound healing in diabetic mice. Mechanistically, MET-Exos upregulated LINC-PINT, which, through competitive binding to miR-139-3p, activated FOXC2, a key regulator of angiogenesis. These data reveal that MET-Exos might promote revascularization and wound healing through the LINC-PINT/miR-139-3p/FOXC2 axis, showing its potential as a therapeutic modality for diabetic wounds.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Pre-metastatic Niche: How Cancer Stem Cell-Derived Exosomal MicroRNA Fit into the Puzzle.","authors":"Behjat Kheiri Yeghaneh Azar, Faezeh Vakhshiteh","doi":"10.1007/s12015-025-10866-z","DOIUrl":"https://doi.org/10.1007/s12015-025-10866-z","url":null,"abstract":"<p><p>Cancer metastasis is a complicated biological process that critically affects cancer progression, patient outcomes, and treatment plans. A significant step in metastasis is the formation of a pre-metastatic niche (PMN). A small subset of cells within tumors, known as cancer stem cells (CSCs), possess unique characteristics including, differentiation into different cell types within the tumor, self-renewal, and resistance to conventional therapies, that enable them to initiate tumors and drive metastasis. PMN plays an important role in preparing secondary organs for the arrival and proliferation of CSCs, thereby facilitating metastasis. CSC-derived exosomes are crucial components in the complex interplay between CSCs and the tumor microenvironment. These exosomes function as transporters of various substances that can promote cancer progression, metastasis, and modulation of pre-metastatic environments by delivering microRNA (miRNA, miR) cargo. This review aims to illustrate how exosomal miRNAs (exo-miRs) secreted by CSCs can predispose PMN and promote angiogenesis and metastasis.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating CD34⁺ Cells: A New Biomarker of Residual Pulmonary Vascular Obstruction after Pulmonary Embolism.","authors":"Nicolas Gendron, Benjamin Planquette, Anne Roche, Richard Chocron, Dominique Helley, Aurélien Philippe, Pierre-Emmanuel Morange, Pascale Gaussem, Olivier Sanchez, David M Smadja","doi":"10.1007/s12015-025-10865-0","DOIUrl":"https://doi.org/10.1007/s12015-025-10865-0","url":null,"abstract":"<p><p>Pulmonary embolism (PE) is a life-threatening condition with long-term complications, including residual pulmonary vascular obstruction (RPVO). RPVO is associated with an increased risk of venous thromboembolism recurrence, chronic symptoms, and reduced quality of life. We hypothesize that an endothelial activation and vascular injury play a central role in the pathophysiology of RPVO. This prospective monocentric study investigates the potential of circulating biomarkers, including CD34⁺ cells, circulating endothelial cells (CECs), and platelet-derived growth factor BB (PDGF-BB), as indicators of vascular sequelae and predictors of RPVO. We included 56 patients with a first episode of PE. Biomarker levels were measured at PE diagnosis and six months later, coinciding with RPVO assessment using ventilation-perfusion lung scans. This defined groups of patients with (RPVO ≥ 10%) and without (RPVO < 10%) perfusion defects. Associations between biomarker levels, presence of perfusion defects, and clinical parameters were analyzed. At PE diagnosis, CEC and PDGF-BB levels were significantly elevated in patients compared to healthy controls, while CD34⁺ levels showed no difference. At the six-month follow-up, patients with perfusion defects exhibited significantly lower CD34⁺ cell levels compared to those without (median 1440 cells/mL vs. 2960 cells/mL). No significant differences in CEC or PDGF-BB levels were observed at follow-up. In conclusion, low CD34⁺ cell levels at RPVO assessment suggest a decreased regenerative potential contributing to thrombus persistence. CD34⁺ cells may serve as biomarkers for perfusion defects and warrant further study for their potential role in guiding clinical management of PE complications.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}